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氯贝丁酯对细胞色素P450同工型CYP4A1的诱导作用与大鼠肝微粒体中乙醇胺特异性磷脂碱基交换反应的激活同时发生。

The induction of cytochrome P450 isoform, CYP4A1, by clofibrate coincides with activation of ethanolamine-specific phospholipid base exchange reaction in rat liver microsomes.

作者信息

Lenart J, Komańska I, Jasińska R, Pikuła S

机构信息

Department of Cellular Biochemistry, M. Nencki Institute of Experimental Biology, Warsaw, Poland.

出版信息

Acta Biochim Pol. 1998;45(1):119-26.

PMID:9701504
Abstract

Administration of a hypolipidaemic drug, clofibrate, to rats resulted, 24 h after a single intraperitoneal injection (250 mg/kg body weight), in pronounced enhancement of the rate of phosphatidylethanolamine (PE) synthesis via the PE-specific base exchange (PEBE) reaction in liver microsomes. This was accompanied by 3.4-fold activation of microsomal omega-hydroxylation of lauric acid by cytochrome P450 4A1 isoform (CYP4A1) and an increase in the protein content of this isoform in endoplasmic reticulum (ER) membranes. Since PE represents a class of phospholipids (PL) prerequisite for proper functioning of CYP4A1, and the PEBE reaction is an inducible pathway of PL synthesis in hepatocytes under metabolic stress, one may speculate that this reaction is switched on when extensive remodelling of PL molecular species or/and massive synthesis of lipid bilayer components for membrane assembly is required.

摘要

给大鼠腹腔注射一次降血脂药物氯贝丁酯(250毫克/千克体重)后24小时,肝脏微粒体中通过磷脂酰乙醇胺特异性碱基交换(PEBE)反应合成磷脂酰乙醇胺(PE)的速率显著提高。这伴随着细胞色素P450 4A1同工型(CYP4A1)对月桂酸微粒体ω-羟基化的3.4倍激活以及内质网(ER)膜中该同工型蛋白质含量的增加。由于PE是CYP4A1正常功能所必需的一类磷脂(PL),且PEBE反应是代谢应激下肝细胞中PL合成的一条可诱导途径,因此可以推测,当需要对PL分子种类进行广泛重塑或/和大量合成用于膜组装的脂质双层成分时,该反应会被开启。

相似文献

1
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